An NPFF receptor antagonist
RF9 is a neuropeptide FF (NPFF) receptor antagonist.1 It binds to human NPFF1 and NPFF2 receptors with Ki values of 58 and 75 nM, respectively. It is selective for NPFF1 and NPFF2 receptors over neuropeptide Y (NPY) receptor Y1, GPR10, GPR54, GPR103, ORL-1, and μ-, δ-, and κ-opioid receptors at 10 μM. RF9 (7.5 μM) inhibits NPFF-induced [35S]GTPγS binding to the NPFF2 receptor. It reverses NPVF-induced inhibition of forskolin-stimulated cAMP accumulation in CHO cells expressing the human NPFF1 receptor (EC50 = 4.7 μM). Intracerebroventricular administration of RF9 (10 μg) inhibits NPFF-induced increases in mean arterial pressure and heart rate in rats. It prevents heroin-induced delayed hyperalgesia and associated tolerance in rats when administered subcutaneously at a dose of 0.1 mg/kg.
1.Simonin, F., Schmitt, M., Laulin, J.-P., et al.RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesiaProc. Natl. Acad. Sci. USA103(2)466-471(2006)
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